The present invention relates to lyophilization or freeze drying and, in particular, to an improved freeze drying apparatus and method which permits the temperature of adjacent shelves to be independently controlled.
Lyophilization is a widely used method for drying a variety of materials, including biological materials, pharmaceutical materials and medical devices, comestibles, and others. Freeze dryers commonly include a freeze drying chamber, shelves in the chamber for holding the product or products to be freeze dried, a condenser, e.g., with refrigeration coils, a vacuum system, and fluid conduits for connecting the various freeze dryer components. Generally, the freeze dryer shelves are cooled and heated during the freeze drying cycle with cooling and heating means, such as a heat exchanger and a heat transfer fluid circulating through the shelves or through tubes lining the shelves.
Typically, the products or materials to be freeze dried are placed in containers (e.g., open or partially opened containers, molds, trays, bags, vials, and so forth), which are then placed on the freeze dryer shelves within the chamber. After the chamber door is closed, the shelves are cooled to freeze the product, typically to about negative 40 degrees Celsius or lower, although higher temperatures may be used (e.g., up to about negative 10 degrees Celsius). Alternatively, one may load onto a pre-frozen shelf. Thermocouples or other temperature probes may be provided to indicate when the product is frozen and at the correct temperature. The freeze dryer chamber and condenser are then evacuated to a deep vacuum using a vacuum pump system, e.g., to a vacuum of about 1 Torr or lower, while vapor condenser coils or plates are cooled, e.g., to around negative 50 degrees Celsius or lower. The shelves are warmed through the controlled addition of heat by circulating a thermal exchange medium through the shelves to provide energy to sublimate the solvent.
The moisture (or other volatile constituents) driven from the product is drawn in vapor form out of the chamber to the condenser, where it condenses and freezes on the condenser coils. Alternatively, the unit may have an internal condenser. This process continues until the product is sufficiently freeze dried as may be determined by known means, after which the chamber is vented to atmospheric pressure, the chamber door is opened, and the freeze-dried product removed.
Commonly, the shelves are arranged in a vertical stack, with a vertical inlet manifold for delivering the thermal fluid to each of the shelf inlets and a vertical outlet manifold arranged on the opposite side of the shelves. The heating and cooling of the product to be freeze dried occurs primarily through conductive heat transfer between the product and the shelf holding the product (and secondarily by convective and radiant heat transfer) and a number of methods have been proposed for minimizing the effect of an adjacent shelf on the product sitting on the shelf below. For example, modular systems have been proposed wherein each shelf or, in some cases each specimen to be lyophilized, is provided with a separate evacuation chamber. Also, it has been proposed to interpose an active or passive heat shield between vertically adjacent lyophilization shelves. The present invention contemplates a new and improved lyophilization apparatus and method which is of simple construction and inexpensive to manufacture, and can be validated for use in regulated production of medical devices and drugs.